Reactive oxygen species (ROS) on Ribosome: from damage to regulation

Emir Behluli; Shefki Xharra; Hilada Nefic; Rifat HadziselimoviC; Gazmend Temaj

doi:10.12923/cipms-2025-0003

Authors

Emir Behluli Departments of Pediatrics, University of Pristina Medical Faculty, Pristina, Kosovo Author https://orcid.org/0000-0002-0889-5510
Shefki Xharra Department of Surgery, Regional Hospital Prizren, Sheh Emin, Prizren, Kosovo Author https://orcid.org/0000-0003-1716-8865
Hilada Nefic Biology, Faculty of Science, University of Sarajevo, Sarajevo, Bosnia and Herzegovina Author https://orcid.org/0000-0002-7774-5743
Rifat HadziselimoviC Biology, Faculty of Science, University of Sarajevo, Sarajevo, Bosnia and Herzegovina Author https://orcid.org/0000-0002-6590-8824
Gazmend Temaj Human Genetics, College UBT, Faculty of Pharmacy Prishtina, Kosovo; University for Business and Technology, Kosovo Author https://orcid.org/0000-0003-4807-2938

DOI:

https://doi.org/10.12923/cipms-2025-0003

Keywords:

cancer diseases, genetic diseases, ribosomopathies, ROS and ribosomal protein, TCA cycle

Abstract

The chemical reactive molecule ROS (Reactive Oxygen Species) is a product of normal cellular metabolism. ROS plays a pivotal role in a wide range of biological processes, including aging, cancer and neurodegenerative diseases. Recent studies have shown that ROS can also affect the ribosomes – molecular machines responsible for protein synthesis. ROS leads to errors in protein synthesis and the production of misfolded proteins, causing damage to ribosomes. However, it has also been suggested that ROS is implicated in the regulation of the ribosome activity under certain conditions. The aim of this paper is to review current knowledge regarding the effects of ROS on ribosomes, with a focus on the mechanisms by which ROS can cause damage to ribosomes and the potential role of ROS in regulating ribosome activity.

References

1. Temaj G, Saha S, Dragusha S, Ejupi V, Buttari B, Profumo E, et al. Ribosomopathies and cancer: pharmacological implications. Expert Rev Clin Pharmacol. 2022;15(6):729-46.

2. Temaj G, Chichiarelli S, Eufemi M, Altieri F, Hadziselimovic R, Farooqi AA, et al. Ribosome-Directed Therapies in Cancer. Biomedicines. 2022;10(9):2088.

3. Temaj G, Hadziselimovic R, Nefic H, Nuhii N. Ribosome biogenesis and ribosome therapy in cancer cells. RRP. 2022;8(4):15-24.

4. Perillo B, Di Donato M, Pezone A, Di Zazzo E, Giovannelli P, Galasso G, et al. ROS in cancer therapy: the bright side of the moon. Exp Mol Med. 2020;52(2):192-203.

5. Kampen KR, Sulima SO, Verbelen B, Girardi T, Vereecke S, Rinaldi G, et al. The ribosomal RPL10 R98S mutation drives IRES-dependent BCL-2 translation in T-ALL. Leukemia. 2019;33(2):319-32.

6. Kampen KR, Fancello L, Girardi T, Rinaldi G, Planque M, Sulima SO, et al. Translatome analysis reveals altered serine and glycine metabolism in T-cell acute lymphoblastic leukemia cells. Nat Commun. 2019;10(1):2542.

7. Yang J, Chen Z, Liu N, Chen Y. Ribosomal protein L10 in mitochondria serves as a regulator for ROS level in pancreatic cancer cells. Redox Biol. 2018;19:158-65.

8. Kim Y, Kim HD, Kim J. Cytoplasmic ribosomal protein S3 (rpS3) plays a pivotal role in mitochondrial DNA damage surveillance. Biochim Biophys Acta. 2013;1833(12):2943-52.

9. Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol. 2014;24(10):453-62.

10. Sullivan LB, Martinez-Garcia E, Nguyen H, Mullen AR, Dufour E, Sudarshan S, et al. The proto-oncometabolite fumarate binds glutathione to amplify ROS-dependent signaling. Mol Cell. 2013;51(2):236-248. doi:10.1016/j.molcel.2013.05.003

11. Ishikawa K, Takenaga K, Akimoto M, Koshikawa N, Yamaguchi A, Imanishi H, et al. ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis. Science. 2008;320(5876):661-4.

12. Woo DK, Green PD, Santos JH, D’Souza AD, Walther Z, Martin WD, et al. Mitochondrial genome instability and ROS enhance intestinal tumorigenesis in APC(Min/+) mice. Am J Pathol. 2012;180(1):24-31.

13. Tubbs A, Nussenzweig A. Endogenous DNA damage as a source of genomic instability in cancer. Cell. 2017;168(4):644-56.

14. Kapralova K, Jahoda O, Koralkova P, Gursky J, Lanikova L, Pospisilova D, et al. Oxidative DNA damage, inflammatory signature, and altered erythrocytes properties in diamond-blackfan anemia. Int J Mol Sci. 2020;21(24):9652.

15. Ravera S, Dufour C, Cesaro S, Bottega R, Faleschini M, Cuccarolo P, et al. Evaluation of energy metabolism and calcium homeostasis in cells affected by Shwachman-Diamond syndrome. Sci Rep. 2016;6:25441.

16. Ambekar C, Das B, Yeger H, Dror Y. SBDS-deficiency results in deregulation of reactive oxygen species leading to increased cell death and decreased cell growth. Pediatr Blood Cancer. 2010;55(6):1138-44.

17. Bezzerri V, Cipolli M. Shwachman-Diamond Syndrome: Molecular mechanisms and current perspectives. Mol Diagn Ther. 2019;23(2):281-90.

18. Zambetti NA, Ping Z, Chen S, Kenswil KJG, Mylona MA, Sanders MA, et al. Mesenchymal Inflammation drives genotoxic stress in hematopoietic stem cells and predicts disease evolution in human pre-leukemia. Cell Stem Cell. 2016;19(5):613-27.

19. Jack K, Bellodi C, Landry DM, et al. rRNA pseudouridylation defects affect ribosomal ligand binding and translational fidelity from yeast to human cells. Mol Cell. 2011;44(4):660-6.

20. Pereboeva L, Westin E, Patel T, Flaniken I, Lamb L, Klingelhutz A, et al. DNA damage responses and oxidative stress in dyskeratosis congenita. PLoS One. 2013;8(10):e76473.

21. Hermanns P, Bertuch AA, Bertin TK, Dawson B, Schmitt ME, Shaw C, et al. Consequences of mutations in the non-coding RMRP RNA in cartilage-hair hypoplasia. Hum Mol Genet. 2005;14(23):3723-40.

22. Aspesi A, Pavesi E, Robotti E, Crescitelli R, Boria I, Avondo F, et al. Dissecting the transcriptional phenotype of ribosomal protein deficiency: implications for Diamond-Blackfan Anemia. Gene. 2014;545(2):282-9.

23. Danilova N, Sakamoto KM, Lin S. Ribosomal protein L11 mutation in zebrafish leads to haematopoietic and metabolic defects. Br J Haematol. 2011;152(2):217-28.

24. Sulima SO, Kampen KR, Vereecke S, Pepe D, Fancello L, Verbeeck J, et al. Ribosomal lesions promote oncogenic mutagenesis. Cancer Res. 2019;79(2):320-7.

25. Landau DA, Tausch E, Taylor-Weiner AN, Stewart C, Reiter JG, Bahlo J, et al. Mutations driving CLL and their evolution in progression and relapse. Nature. 2015;526(7574):525-30.

26. Xia J, Miller CA, Baty J, Ramesh A, Jotte MRM, Fulton RS, et al. Somatic mutations and clonal hematopoiesis in congenital neutropenia. Blood. 2018;131(4):408-16.

27. Willi J, Küpfer P, Evéquoz D, Fernandez G, Katz A, Leumann C, et al. Oxidative stress damages rRNA inside the ribosome and differentially affects the catalytic center. Nucleic Acids Res. 2018;46(4):1945-57.

28. Netzer N, Goodenbour JM, David A, Dittmar KA, Jones RB, Schneider JR, et al. Innate immune and chemically triggered oxidative stress modifies translational fidelity. Nature. 2009;462(7272):522-6.

29. Mills EW, Green R. Ribosomopathies: There’s strength in numbers. Science. 2017;358(6363):2755.

30. Sulima SO, De Keersmaecker K. Bloody mysteries of ribosomes. Hemasphere. 2018;2(5):e95.

31. Richardson C, Yan S, Vestal CG. Oxidative stress, bone marrow failure, and genome instability in hematopoietic stem cells. Int J Mol Sci. 2015;16(2):2366-85.

32. Simsek D, Tiu GC, Flynn RA, Byeon GW, Leppek K, Xu AF, et al. The mammalian ribo-interactome reveals ribosome functional diversity and heterogeneity. Cell. 2017;169(6):1051-65.

33. Kang J, Brajanovski N, Chan KT, Xuan J, Pearson RB, Sanij E. Ribosomal proteins and human diseases: molecular mechanisms and targeted therapy. Signal Transduct Target Ther. 2021;6(1):323.

34. Scott KEN, Cleveland JL. Lactate wreaks havoc on tumor-infiltrating T and NK Cells. Cell Metab. 2016;24(5):649-50.

35. Avondo F, Roncaglia P, Crescenzio N, Krmac H, Garelli E, Armiraglio M, et al. Fibroblasts from patients with Diamond-Blackfan anaemia show abnormal expression of genes involved in protein synthesis, amino acid metabolism and cancer. BMC Genomics. 2009;10:442.

36. Calamita P, Gatti G, Miluzio A, Scagliola A, Biffo S. Translating the game: ribosomes as active players. Front Genet. 2018;9:533.

37. Topf U, Suppanz I, Samluk L, Wrobel L, Böser A, Sakowska P, et al. Quantitative proteomics identifies redox switches for global translation modulation by mitochondrially produced reactive oxygen species. Nat Commun. 2018;9(1):324.

38. Le Moan N, Clement G, Le Maout S, Tacnet F, Toledano MB. The Saccharomyces cerevisiae proteome of oxidized protein thiols: contrasted functions for the thioredoxin and glutathione pathways. J Biol Chem. 2006;281(15):10420-30.

39. Go YM, Duong DM, Peng J, Jones DP. Protein cysteines map to functional networks according to steady-state level of oxidation. J Proteomics Bioinform. 2011;4(10):196-209.

40. Xie K, Bunse C, Marcus K, Leichert LI. Quantifying changes in the bacterial thiol redox proteome during host-pathogen interaction. Redox Biol. 2019;21:101087.

41. Brandes N, Reichmann D, Tienson H, Leichert LI, Jakob U. Using quantitative redox proteomics to dissect the yeast redoxome. J Biol Chem. 2011;286(48):41893-903.

42. Knoefler D, Thamsen M, Koniczek M, Niemuth NJ, Diederich AK, Jakob U. Quantitative in vivo redox sensors uncover oxidative stress as an early event in life. Molecular Cell. 2012;47(5):767-76.

43. Menger KE, James AM, Cochemé HM, Harbour ME, Chouchani ET, Ding S, et al. Fasting, but not aging, dramatically alters the redox status of cysteine residues on proteins in drosophila melanogaster. Cell Rep. 2015;13(6):1285.

44. Davies MJ. Protein oxidation and peroxidation. Biochem J. 2016;473(7):805-25.

45. Groitl B, Jakob U. Thiol-based redox switches. Biochim Biophys Acta. 2014;1844(8):1335-43.

46. Stadtman ER, Levine RL. Free radical-mediated oxidation of free amino acids and amino acid residues in proteins. Amino Acids. 2003;25(3-4):207-18.

47. Nyström T. Role of oxidative carbonylation in protein quality control and senescence. EMBO J. 2005;24(7):1311-7.

48. Ezraty B, Gennaris A, Barras F, Collet JF. Oxidative stress, protein damage and repair in bacteria. Nat Rev Microbiol. 2017;15(7):385-96.

49. Lemma-Gray P, Weintraub ST, Carroll CA, Musatov A, Robinson NC. Tryptophan 334 oxidation in bovine cytochrome c oxidase subunit I involves free radical migration. FEBS Lett. 2007;581(3):437-42.

50. Taylor SW, Fahy E, Murray J, Capaldi RA, Ghosh SS. Oxidative post-translational modification of tryptophan residues in cardiac mitochondrial proteins. J Biol Chem. 2003;278(22):19587-90.

51. Todorovski T, Fedorova M, Hoffmann R. Mass spectrometric characterization of peptides containing different oxidized tryptophan residues. J Mass Spectrom. 2011;46(10):1030-8.

52. Bollineni RC, Hoffmann R, Fedorova M. Proteome-wide profiling of carbonylated proteins and carbonylation sites in HeLa cells under mild oxidative stress conditions. Free Radic Biol Med. 2014;68:186-95.

53. Barrera G, Pizzimenti S, Daga M, Dianzani C, Arcaro A, Cetrangolo GP, et al. Lipid peroxidation-derived aldehydes, 4-hydroxynonenal and malondialdehyde in aging-related disorders. Antioxidants (Basel). 2018;7(8):102.

54. Williams MS, Hermanns P. Analysis ofRPS19 in patients with cartilage-hair hypoplasia and severe anemia: Preliminary results. Am J Med Genet. 2005;138A(1):66-7.

Reactive oxygen species (ROS) on Ribosome: from damage to regulation

Authors

DOI:

Keywords:

Abstract

References

Downloads

Published

Issue

Section

License

How to Cite

sidebar

Language